Guidance on mucositis assessment from the MASCC Mucositis Study Group and ISOO: an international Delphi study.

Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022-July 2023). The first phase involved a survey to MASCC-MSG members (January 2022-May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023-May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Immediate pain alleviation in oral mucositis and other oral ulcerative diseases through photobiomodulation therapy: the preemptive treatment concept.

OBJECTIVE: Photobiomodulation therapy is recommended by multiple international societies for managing oral mucositis. These recommendations are based on extensive evidence. However, the search for an optimal photobiomodulation protocol continues. This mapping review focuses on a novel aspect of photobiomodulation therapy which is the immediate effect on pain levels associated with oral ulcerative conditions. DATA SOURCES: This literature review systematically compiles and evaluates the evidence about oral mucositis, alongside other oral ulcerative conditions, as the protocols that achieved pain relief for these oral conditions may have potential applicability to oral mucositis management. The scientific database used was PubMed. CONCLUSION: Whereas most of the randomized controlled trials about photobiomodulation therapy for oral mucositis and other ulcerative oral diseases reported delayed pain relief, certain photobiomodulation therapy protocols reported immediate pain relief. The results of this review highlight the concept of preemptive photobiomodulation therapy, in which photobiomodulation therapy is delivered early in the development of oral mucositis throughout the oncotherapy and may achieve immediate pain relief consistently in most of the patients and close to a negligible pain level. Photobiomodulation therapy, as a powerful nonpharmacologic tool for immediate pain relief, has a great beneficial value in patients suffering from oral mucositis and other painful oral ulcerative diseases such as recurrent aphthous stomatitis and chronic graft-versus-host disease.

Late recurrence of Burkitt's lymphoma in the jaw: numb chin syndrome as the only symptom

The Numb Chin Syndrome (NCS) is defined as facial and oral numbness restricted to the mental nerve's distribution involving the lower lip, skin of the chin, or gingiva of the lower anterior teeth. Hypoesthesia can occur unilaterally or bilaterally. Although this syndrome is rare, its importance is related to the fact that it represents the clinical manifestations of malignant diseases. Breast cancer and non-Hodgkin lymphoma are the most common cause of NCS. The patient, a 58-year-old woman, treated for a Burkitt Lymphoma (BL) nine years ago, described a two-week history of change in sensitivity and pain in the chin region, without relief with the use of analgesics. She had no headache, speech disturbance, dysphagia, visual disturbance, or other neurological symptoms. No surgical intervention has been performed recently. The intraoral examination revealed a healthy oral mucosa and a small area adjacent to the right mental nerve region that was uncomfortable to palpation. No changes were found in the bone trabeculae at cone-beam computed tomography. The contrasted magnetic resonance features made it possible to identify a change in the mandibular body extending to the entire right side, coinciding with the patient's complaint, indicating a probable mandibular medullary invasion. The patient was submitted to a biopsy to rule out a possible recurrence of BL. The microscopic findings were consistent with the diagnosis of BL. The present report described a very unusual presentation of late recurrent BL nine years after the first treatment, which manifested as an NCS.

Myeloid sarcoma in the tongue

Leukemic cells are rarely present in the oral cavity, and there are very few reports regarding such cases. However, we identified some reports of leukemic cells infiltrating tissues in the oral cavity, including gingival involvement. Recurrent painful oral ulcerations and prominent generalized periodontal destruction are the most common oral features of neutrophil disorders, and they may even be the initial symptoms of the disease. The ulcers may affect any part of the oral mucosa, including the tongue and palate. The objective of this report is to describe and discuss a case of myeloid sarcoma in the oral cavity of a 48-year-old male patient.

Clinicopathological and ultrastructural characterization of periapical actinomycosis

BACKGROUND: The aim of the present study was to analyze the clinicopathological and the ultrastructural features of periapical actinomycosis (PA) cases. MATERIAL AND METHODS: Data from the files of an oral pathology laboratory were retrieved and the findings of histopathological analysis were evaluated. Hematoxylin-eosin (HE), a modified Brown & Brenn, and Grocott stains as well as ultrastructural analysis using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) were utilized. RESULTS: Six cases were obtained, 4 females and 2 males, with a mean age of 34 year-old. Two cases were symptomatic, lower teeth and the anterior region were more commonly affected, and all cases were characterized by periapical radiolucencies. All cases presented sulfur granules with a ray-fungus or club-shaped pattern of the Splendore-Hoeppli phenomenon in HE-stained sections, with filamentous gram-positive bacteria aggregates highlighted by the modified Brown & Brenn stain. SEM analysis revealed abundant packed rod-like and filamentous bacteria associated with an extracellular amorphous material. EDX analysis showed predominant picks of calcium and sulfur in actinomycotic colonies. CONCLUSIONS: Our findings suggest that PA manifests either clinically and radiologically as a non-specific and heterogeneous condition and that the actinomycotic colonies consist in a calcium- and sulfur-rich matrix. Furthermore, the results highlight the importance of submitting periapical specimens after surgical removal to histopathological análisis

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Linicopathological analysis of head and neck rhabdomyosarcoma: A series of 10 cases and literature review

Background: To describe the clinicopathological characteristics of a series of head and neck rhabdomyosarcoma (RMS) and to review the literature. Material and Methods: Cases diagnosed as RMS affecting the head and neck region were retrospectively retrieved from the files of two Brazilian institutions from January 2006 to January 2017. Data on clinical features (sex, age and affected site), microscopic subtype, immunohistochemical results, treatment employed and follow-up status were obtained from the patient's medical charts. Results: During the period considered, 10 cases of RMS were identified. Females predominated (4M:6F), the mean age at diagnosis was 16.5 years-old and the orbit was the most affected site (4 cases). Microscopically, most cases were classified as embryonal RMS (6 cases) and the Desmin/Myogenin/Myo-D1 immunohistochemical positivity was useful to confirm the diagnosis. Chemotherapy and radiotherapy were applied to 9 and 8 patients respectively, whereas 2 patients were treated by surgery. Recurrences occurred in 3 patients and distant metastasis in 2 cases. Nine patients were alive in their last follow-up, 3 of them with disease, whereas 1 patient died due to the disease. Conclusions: Head and neck RMS is an aggressive malignant neoplasm which demands especial concern to achieve early diagnosis and successful treatment (AU)

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Surgery Combined with LPRF in Denosumab Osteonecrosis of the Jaw: Case Report

Abstract This paper describes two cases in which the use of leucocyte-rich and platelet-rich fibrin (LPRF) combined with bone resection did not result in complete tissue response in the treatment of medication-related osteonecrosis of the jaw (MRONJ). It has been recently described in patients receiving subcutaneous administration of RANK-inhibitors, such as Denosumab, and anti-angiogenic drugs, such as Bevacizumab, as observed in our cases. Due to promising results in recent studies, more patients will receive these medications in order to avoid skeletal complications due to metastatic bone disease and, therefore, this scenario has a potential to become a comparable challenge to the bisphosphonate- induced jaw necrosis in the area of Oral and Maxillofacial Surgery. No convincing surgical technique has been described to overcome the non-healing mucosal lesions with exposed bone due to RANK-inhibitor therapy. Based on the findings in the literature and in both cases described herein can be concluded that the use of LPRF should be considered in the treatment of patients with DRONJ.

Resumo Este artigo descreve dois casos onde a ressecção óssea associada à fibrina rica em plaquetas e leucócitos (LPRF) não resultou em resposta completa no tratamento da osteonecrose dos maxilares relacionados à medicações (MRONJ). Como observado nos casos aqui relatados, MRONJ foi recentemente descrito na literatura em pacientes que recebem a administração subcutânea de inibidores-RANK, como Denosumab ou drogas anti-angiogenicas, como Bevacizumab. Estudos recentes com resultados promissores indicam que mais pacientes serão tratados com estas terapias para evitar complicações esqueléticas devido às metástases ósseas. Portanto, este cenário pode tornar-se um desafio clínico comparável às osteonecroses dos maxilares relacionados aos bisfosfonatos na área de Cirurgia Bucomaxilofacial. Até o momento, nenhuma técnica cirúrgica foi descrita com eficiência para superar as lesões da mucosa com exposição óssea e que não cicatrizam devido a terapia com inibidores de RANK. Com base na literatura e nos achados dos casos reportados, podemos concluir que o uso do LPRF pode ser considerado no tratamento de pacientes com osteonecrose dos maxilares relacionados ao Denosumab.

Immunohistochemical expression of p63, epidermal growth factor receptor (EGFR) and notch-1 in radicular cysts, dentigerous cysts and keratocystic odontogenic tumors

The aim of this study was to assess the immunohistochemical expression of p63 protein, epidermal growth factor receptor (EGFR) and Notch-1 in the epithelial lining of radicular cysts (RC), dentigerous cysts (DC) and keratocystic odontogenic tumors (KOT). For this study, 35 RC, 22 DC and 17 KOT were used. The clinical and epidemiological data were collected from the patient charts filed in the Oral Pathology Laboratory, University of Ribeirão Preto, Brazil. Immunohistochemical reactions against the p63, EGFR and Notch-1 were performed in 3-µm-thick histological sections. The slides were evaluated according to the following criteria: negative: <5% of positive cells, low expression: 5-50% of positive cells, and high expression: >50% of positive cells. Moreover, the intensity of EGFR and Notch-1 expressions was also evaluated. Fisher's exact test and Spearman's correlation coefficients were used for statistical analysis, considering a significance level of 5%. Almost all cases demonstrated p63, EGFR and Notch-1 expressions. The p63 expression was significantly higher in KOT (p<0.001). Positive correlation between these immunomarkers was observed. These findings suggest the participation of p63, EGFR and Notch-1 in the development, maintenance and integrity of cystic odontogenic epithelial lining, favoring lesion persistence. The high expression of p63 in KOT suggests that it may be related to their more aggressive biological behavior and marked tendency to recurrence.

O objetivo deste estudo foi avaliar a expressão imunoistoquímica da proteína p63, receptor do fator de crescimento epidérmico (EGFR) e Notch-1 no revestimento epitelial de cistos radiculares (CR), cistos dentígeros (CD) e tumores odontogênicos queratocísticos (TOQ). Para este estudo, 35 CR, 22 CD e 17 TOQ foram utilizados. Os dados clínicos e epidemiológicos foram coletados das fichas dos pacientes arquivadas no Laboratório de Patologia Oral, Universidade de Ribeirão Preto, Brasil. Reações imunoistoquímicas contra p63, EGFR e Notch-1 foram realizadas em cortes histológicos de 3 µm. As lâminas foram avaliadas de acordo com os seguintes critérios: negativo <5% das células positivas, baixa expressão - 5%-50% das células positivas e alta expressão >50% das células positivas. Além disso, a intensidade de expressão de EGFR e Notch-1 foi também avaliada. Teste exato de Fisher e coeficiente de correlação de Spearman foram usados para análise estatística, considerando um nível de significância de 5%. Quase todos os casos demonstraram expressão de p63, EGFR e Notch-1. A expressão de p63 foi significativamente maior nos TOQ (p<0.001). Correlação positiva entre os imunomarcadores foi observada. Esses achados sugerem a participação de p63, EGFR e Notch-1 no desenvolvimento, manutenção e integridade do revestimento epitelial cístico, favorecendo a persistência das lesões. A alta expressão de p63 no TOQ sugere que ela pode estar relacionada ao comportamento biológico mais agressivo e marcada tendência a recorrência.

Syndecan-1 (CD138) and Ki-67 expression in odontogenic cystic lesions

The aim of this study was to assess the immunohistochemical expression of syndecan-1 (CD138) and Ki-67 in radicular cysts (RC), dentigerous cysts (DC) and keratocystic odontogenic tumors (KOT). Thirty-five RC, 22 DC and 17 KOT were used in the study and immunohistochemical reactions using anti-syndecan-1 and anti-Ki-67 antibodies were performed by the streptavidin-biotin-peroxidase method. Fisher's exact test and Spearman's correlation coefficient were used for statistical analysis of data. Among the studied lesions, no differences in the syndecan-1 expression were observed, but the suprabasal expression of Ki-67 was significantly higher in KOT (p<0.0001), when compared with RC and DC. In RC, there was positive correlation between the expression (p=0.02) and intensity (p=0.0001) of syndecan-1 and between the intensity of syndecan-1 and Ki-67 expression (p=0.01). In the KOT, Ki-67 expression in the suprabasal layer correlated positively with the expression (p=0.01) and intensity (p=0.01) of syndecan-1. The expression of syndecan-1 does not seem to be a determinant factor of the distinct histopathological features and biological behavior of the studied lesions. Nevertheless, positive correlation between syndecan-1 and a cell proliferation marker was observed in RC and KOT.

O objetivo deste estudo foi avaliar a expressão imunoistoquímica de syndecan-1 (CD138) e Ki-67 em cistos radiculares (CR), cistos dentígeros (CD) e tumores odontogênicos queratocísticos (TOQ). Trinta e cinco CR, 22 CD e 17 TOQ foram utilizados no estudo e as reações imunoistoquímicas usando os anticorpos anti-syndecan-1 e anti-Ki-67 foram realizadas pelo método estreptavidina-biotina-peroxidase. Para análise estatística, o teste exato de Fisher e o coeficiente de correlação de Spearman foram utilizados. Entre as lesões estudadas, não foram observadas diferenças na expressão de syndecan-1, mas a expressão suprabasal de Ki-67 foi significativamente maior nos TOQ (p<0,0001), quando comparado aos CR e CD. No CR, havia correlação positiva entre a expressão (p=0,02) e intensidade (p=0,0001) de syndecan-1 e entre a intensidade de syndecan-1 e expressão de Ki-67 (p=0,01). No TOQ, a expressão de Ki-67 na camada suprabasal correlacionou positivamente com a expressão (p=0,01) e intensidade de expressão (p=0,01) de syndecan-1. A expressão de syndecan-1 não parece ser um fator determinante das características histopatológicas distintas e do comportamento biológico das lesões estudadas. Entretanto, correlação positiva entre syndecan-1 e um marcador de proliferação celular foi evidenciado em CR e TOQ.

Estudo clínico, radiográfico, microscópico e perfil imunoistoquímico dos ameloblastomas: a experiência do Hospital A. C. Camargo / Clinico radiographic, histologic and immunohistochemical study of ameloblastomas: the A. C. Camargo Hospital experience

Os Ameloblastomas são tumores odontogênicos que exibem crescimento lento, porém mostram-se localmente agressivos. Este estudo teve como objetivo avaliar e correlacionar os achados clínico-radiográficos, histopatológicos e a expressão imunoistoquímica de diversos marcadores em Ameloblastomas e estabelecer informações relevantes quanto biologia, tratamento e prognóstico deste tumor. ... Os dados foram analisados estatisticamente usando os testes estatísticos apropriados, dentre eles o método de Kaplan-Meyer e a regressão logística de Cox. ... A análise estatística univariada mostrou que o aspecto radiográfico multilocular, a presença de corticais ósseas rompidas e o aspecto histológico folicular indicaram maior chance de recorrência. ... Podemos concluir que o ameloblastoma mostrou distribuição semelhante entre os gêneros, predominância na quarta e quinta décadas de vida na região posterior de mandíbula. O padrão sólido foi o mais comum e radiograficamente estes casos exibiram predominantemente o padrão multilocular com aumento estatisticamente significativo na incidência de rescidivas quando comparado aos casos sólidos uniloculares. A presença de cortical mandibular perfurada também indicou um maior risco para a recorrência (6,5 vezes). O epitélio dos ameblastomas foi itensamente positivo para as citoqueratinas AE1AE3, 34β12, 14 e 19. O tempo de queixa com positividade para Syndecan-1 foi estatisticamente menor do que os casos negativos. Além disso, os ameloblastomas mostram imunopositividade para EGFr e PTHrP.

Ameloblastomas are benign odontogenic tumors that exhibit slow growth, but have shown to be locally aggressive. The aim of this study was to evaluate and correlate the clinical-radiographic, histopathologic findings and immunohistochemical expression of various markers in Ameloblastomas and establish relevant information regarding biology, treatment and prognosis of this tumor. This was a retrospective study of 121 cases of Ameloblastomas diagnosed and treated at the "Hospital A.C.Camargo" between 1953 and 2003. All cases were confirmed histologically, classified and a selection of areas for the Tissue Microarray were done. Antibodies were analyzed to investigate prognostic and cell proliferation factors, (anti Ki-67; p53, EGFR, Syndecan-1 (CD 138), PTHrP) and to investigate the tumoral histogenesis (vimentin and cytokeratins Ck 1, 4, 6, 7, 8, 10, 14, 16, 18, 19 and 34ß andAE1/AE3). The data ere statistically analyzed using the appropriate statistical tests, among them twhe Kaplaars) n-Meyer method and Cox logistic regression. Patients' ages ranged from 02 to 82 years (mean = 33.2 ye with slight predilection for females. The majority of cases affected the posterior region of the mandible (80%) Radiographically, 60% showed multilocular pattern. Solid Ameloblastomas accounted for 113 cases, and the plexiform histologic type was the commonest. Solid tumors were treated by resection in block, curettage associated with cryotherapy, or only curettage, and unicystic tumors only by conservative procedures. The global recurrence rate was 22.1% with a mean follow-up time of 9.7 years. Univariate statistical analysis showed that the radiographic multilocular aspect, presence of ruptured bone corticals and the follicular histologic aspect indicated greater chance of recurrence. Positivity for cytokeratins AE1/AE3, 34ß12, 14 and 19 and negativity for cytokeratins 1 and 10 strengthened their odontogenic profile. The innumerable histologic subtypes and great variability of cellular differentiation in each tumor makes some cytokeratins, such as CKs 6,7, 8, 16 and 18 and vimentin show focal and specific expressions. Syndecan-1 howed negativity for 18.2% and weak positivity for 42.1% weak positivity for it. In the evaluation for Ki67, the majority of the samples of the cases. It showed statistically significant association with the time of complaint, in other words, cases positive for this marker showed a shorter time of complaint than the cases in which Syndecan-1 was negative. EGFR was expressed in the majority of cases, irrespective of the histologic subtype, but showed no association with any clinical and radiographic parameter. PTHrP showed 100% positivity in our casuistic and statistical analysis showed that patients with strong positivity for this marker were at an older age than patients with presented marking between 0-25% of tumoral cells. The marker p53 showed positivity in 82.5% of the cases and of these, 40.7% with immunoreactivity between 51-100% of the tumoral cells. In conclusion, ameloblastoma showed similar gender distribuition, most of the cases occured in the fourth and fifth decades and the majority affected the posterior region of the mandible.The solid pattern was the most common and, radiographically those cases were predominantely multilocular. The multilocular pattern showed a statistically higher tendendy to recurrence when compared to the solid unilocular type. Moreover, a perforated osseous cortical increased 6.5X the chance for recurrence. Tipically, the Ameloblastoma epithelium was positive for citokeratins AE1AE3, 34ß12, 14 and 19. The time of complain for the positives cases of Syndecan-1 were statistically lower when compared to the negative cases and solid ameloblastomas were positive for EGFr and PTHrP.

Leucoplasia pilosa oral no contexto atual da AIDS / Oral hairy leukoplakia in the current context of the AIDS

A leucoplasia pilosa é uma lesão especifica da mucosa oral frequentemente observada em borda lateral de lingua de pacientes HIV positivos. O seu aparecimento é indicativo de infecção inicial pelo HIV e progressão da doenca para AIDS. Esta fortemente associada a imunodepressao grave (contagem de linfócitos T CD4+< 200 celulas/ml). Acredita-se que a lesão seja resultado de uma infecção pelo virus Epstein-Barr(EBV) nas células epiteliais. Clinicamente, é caracterizada por uma placa branca, elevada, corrugada, não removível à raspagem, assintomática e acometendo, preferencialmente, a borda lateral da lingua bilateralmente. Histologicamente observa-se acantose, hiperparaqueratose, células balonizantes na camada espinhosa do epitélio com inclusões virais intranucleares e ausência de infiltrado inflamatório subepitelial. Em cerca de 30 porcento dos casos pode-se observar pseudo-hifas de Candida sp na camada de paraqueratina. O diagnostico definitivo da lesão é feito pela demonstração do virus.

Carcinoma espinocelular bucal e suas variantes / Buccal squamous cell carcinoma and its variants

O carcinoma espinocelular (CEC) é a principal neoplasia maligna que acomete a cavidade bucal. O CEC bucal apresenta cinco variantes, as quais mostram características histológicas, comportamento clínico e resposta ao tratamento distintas. O cirurgiäo-dentista deve estar apto a identificar as características clínicas, histopatológicas, etiopatogênicas, modalidades terapêuticas e prognóstico dos CECs bucais, propiciando a realizaçäo de diagnóstico precoce e tratamento de suporte adequado aos pacientes. Neste artigo, apresentamos uma breve revisäo da literatura abordando os principais aspectos do CEC e suas variantes